Metabolism of zinc and copper in the neonate: accumulation and function of (Zn, Cu)-metallothionein in the liver of the newborn rat.

1. Measurements were made of the hepatic concentrations and contents of total and thionein-bound zinc and copper in late foetal and newborn rats and of the distribution of these metals between the particulate and soluble components of the liver. 2. The decrease in the hepatic concentration of thionein-bound Zn, which occurred with age after birth, was proportional to the increase in liver weight until the 16th day post partum; thereafter it was greater. 3. Throughout the period from birth to 25 d of age the Zn concentration remained constant in the cytosolic non-thionein fraction (i.e. total cytoplasmic Zn--thionein-bound Zn), but decreased in other compartments of the liver. 4. The same constant concentration of cytoplasmic non-thionein-bound Zn also was observed in animals with reduced total hepatic Zn contents, but normal body-weights, and in 20-d-old Zn-deficient pups. 5. The concentration of thionein-bound Cu increased significantly only between the 6th and 14th day post partum. The age-related variations in Cu contents of the particulate components closely paralleled those in the whole liver, whereas the Cu contents of the cytosolic thionein and non-thionein fractions did not increase appreciably until after the 10th day. 7. It is concluded that the cytosolic non-thionein fraction of newborn rat liver may contain particularly important metabolic sites that require Zn and a major function of Zn-thionein is to regulate the supply of the metal to these sites. As, from birth to 26 d of age, the sum of the concentrations of thionein-bound Zn and Cu was correlated with whole liver Zn, the accumulation of Cu as a soluble metallothionein seems to be a secondary event, dependent on the hepatic Zn concentration.